Association between the APOA2 promoter polymorphism and body weight in Mediterranean and Asian populations: replication of a gene-saturated fat interaction

Objective: The APOA2 gene has been associated with obesity and insulin resistance (IR) in animal and human studies with controversial results. We have reported an APOA2-saturated fat interaction determining body mass index (BMI) and obesity in American populations. This work aims to extend our findings to European and Asian populations. Methods: Cross-sectional study in 4602 subjects from two independent populations: a high-cardiovascular risk Mediterranean population (n = 907 men and women; aged 67 +/- 6 years) and a multiethnic Asian population (n = 2506 Chinese, n = 605 Malays and n = 494 Asian Indians; aged 39 +/- 12 years) participating in a Singapore National Health Survey. Anthropometric, clinical, biochemical, lifestyle and dietary variables were determined. Homeostasis model assessment of insulin resistance was used in Asians. We analyzed gene-diet interactions between the APOA2 = 265T > C polymorphism and saturated fat intake (< or >= 22 g per day) on anthropometric measures and IR. Results: Frequency of CC (homozygous for the minor allele) subjects differed among populations (1-15%). We confirmed a recessive effect of the APOA2 polymorphism and replicated the APOA2-saturated fat interaction on body weight. In Mediterranean individuals, the CC genotype was associated with a 6.8% greater BMI in those consuming a high (P - 0.018), but not a low (P = 0.316) saturated fat diet. Likewise, the CC genotype was significantly associated with higher obesity prevalence in Chinese and Asian Indians only, with a high-saturated fat intake (P = 0.036). We also found a significant APOA2-saturated fat interaction in determining IR in Chinese and Asian Indians (P 0.026). Conclusion: The influence of the APOA2 -265T > C polymorphism on body-weight-related measures was modulated by saturated fat in Mediterranean and Asian populations. International Journal of Obesity (2011) 35, 666-675; doi: 10.1038/ijo.2010.187; published online 26 October 2010